Tumor-targeted delivery of tetanus toxoid by Listeria reduces glioblastomas in mice

Malignant brain cancer is one of the most difficult cancers to treat. This is partly due to the inability of drugs or immune cells to pass the blood brain barrier (BBB), resulting in reduced success of therapy. Moreover, glioblastoma multiforme (GBM) is particularly aggressive and treatment resistant. Our preliminary results show that Listeria-based immunotherapy is very promising and pass the BBB. In this project we will analyze Listeria-TT+Gemcitabine treatments in various models with GBM. In Aim 1, we will characterize Listeria-TT in brain tumors in vivo and in vitro, which include the biodistribution in vivo, and infection and kill of tumor cells in vitro. In Aim 2, we will analyze the efficacy and survival of the GBM mice treated with Listeria-TT+GEM. While many experiments occur in vitro in this project, certain experiments need animals. For instance, it is important to measure the side effects of Listeria in vivo. Listeria treatments may lead to Listeriosis, hepatic impairment, and particularly in the brain it is important to measure how long Listeria can survive and do not give chronic infections in the brain. These are the experiments the FDA asks. Such experiments cannot be mimicked in vitro. Moreover, Listeria behaves different in vivo compared to in vitro. In vitro, Listeria abundantly infects and kill normal cells but not in vivo. This is because Listeria is rapidly eliminated by the immune system in normal tissues, but in vitro there is no immune system and thus Listeria can easily infect and kill the normal cells. Thus, using in vitro experiments only, would have led to complete wrong hypotheses. Project Number: 1R21CA303427-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: CLAUDIA GRAVEKAMP | Institution: ALBERT EINSTEIN COLLEGE OF MEDICINE, BRONX, NY | Award Amount: $431,970 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 CDPT-Y (56)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11374090